IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B

Lampertico, Pietro; Viganò, Mauro; Cheroni, Cristina; Facchetti, F.; Invernizzi, Federica; Valveri, V.; Soffredini, R.; Abrignani, Sergio; Francesco, Raffaele De; Colombo, Massimo

doi:10.1002/hep.25749

Cited by 156 publications

(138 citation statements)

References 35 publications

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“…Oddly, this allele was described as a negative predictive factor of PegIFN/RBV efficacy in chronic hepatitis C. Such configuration of alleles, taking into account race differences (more frequent in Caucasians, rare in Japanese and very rare in Chinese Han race) may explain the better response to treatment in chronic hepatitis C caused by genotype 1 in a Far East population, whereas the response to therapy of CHB behaves contrariwise. Lampertico et al [22] analyzed a group of 101 Caucasians infected with HBV genotype D, treated with recombined IFN or PegIFN for an average of 23 months with median follow-up of 11 years. Loss of HBsAg with or without anti-HBs development was considered as the study endpoint.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

Pleśniak¹,

Wawrzynowicz‐Syczewska²

2017

Arch Med Sci Civil Dis

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A b s t r a c tIntroduction: Because of its worldwide prevalence, chronic hepatitis B constitutes a significant global health issue. Chronic hepatitis B virus (HBV) infection affects about 350 million people, with 1 million deaths annually due to its sequelae. The unique way of replication makes HBV difficult to eradicate with the available treatment. Interferon is currently the only option offering a "curative treatment strategy". Predictors of a sustained response to interferon are desired. The aim of this study was to assess the efficacy of chronic hepatitis B treatment with pegylated interferon α2a in relation to the polymorphisms of the interleukin 28B gene. Material and methods: Eighty-six patients were included in the study. They were treated with PegIFNα2a in the dose of 180 µg weekly for 48 weeks and were followed up for at least 1 year after the end of therapy (EOT). Treatment efficacy was defined as HBsAg clearance or HBV viral load ≤ 2000 IU/ml at the end of therapy and at the end of 12 consecutive months. Two polymorphisms of IL28B at loci rs12979860 and rs809997 were examined in every patient. Results: No associations between any of the IL28B polymorphisms and HBsAg elimination were found. However, a weak but statistically significant association between persistent HBV-DNA decrease and a TT variant (C/T) of IL28B was found (Spearman's correlation coefficient 0.236, p < 0.001). Patients having this polymorphism also had significantly lower HBV-DNA loads after EOT (Spearman's correlation coefficient 0.27, p = 0.02). The weak associations and small number of patients do not allow us to draw firm conclusions. Conclusions: We discovered no associations between any of the IL28B polymorphisms and HBsAg loss, IL28B polymorphisms do not seem to play an important role as predictors of treatment efficacy in the treatment of chronic B hepatitis with pegylated interferon.

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Section: Discussionmentioning

confidence: 99%

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

Pleśniak¹,

Wawrzynowicz‐Syczewska²

2017

Arch Med Sci Civil Dis

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“…12,13 Less favorable results were obtained for patients infected with hepatitis B virus (HBV). Although in some studies, the CC genotype of rs12979860 was an independent predictor of HBsAg seroclearance by interferon therapy, 14 and patients with this genotype were found to have more frequently lower viral load levels, 15 a recent meta-analysis by Tang et al 16 has not found any association between IFNL3 rs12979860 C/T and the risk of persistent HBV infection.…”

Section: 4mentioning

confidence: 98%

Effect of interferon λ3 gene polymorphisms, rs8099917 and rs12979860, on response to hepatitis B virus vaccination and hepatitis B or C virus infections among hemodialysis patients

Grzegorzewska¹,

Jodłowska²,

Mostowska³

et al. 2015

Polish Archives of Internal Medicine

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IntroductIon The higher prevalence and risk of hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are still observed in hemodialysis (HD) patients compared with healthy people. Interferons (IFNs) are known for their involvement in immune response. The addition of IFN-λ3 to immunization in animal models was shown to increase the immune response of T helper-1 cells.objectIves We studied whether polymorphisms of the IFN-λ3 gene (IFNL3) might be associated with the development of antibodies to HBV surface antigen [anti-HBs] in response to the HBV vaccination or HBV infection as well as spontaneous resolution of HCV infection in HD patients. PAtIents And methodsThe HD group consisted of 806 individuals without a history of HBV or HCV infection (of whom 672 developed anti-HBs in response to the HBV vaccination), 241 HBV-infected patients (of whom 186 developed anti-HBs), and 63 HCV-infected patients (including 39 HCV RNA-positive subjects). All patients were genotyped for IFNL3 rs8099917 and rs12979860 polymorphisms using a high-resolution melting curve analysis.results The comparison of responders and nonresponders to HBV vaccination revealed no significant differences in the IFNL3 genotype distribution. In HBV-infected patients, the differences in the distribution of IFNL3 variants between anti-HBs-negative and anti-HBs-positive patients were also nonsignificant. Spontaneous HCV clearance was significantly less common in the carriers of the rs8099917 allele G or rs12979860 allele T, while the CT rs12979860_rs8099917 haplotype was more frequent (P = 0.02) in patients showing spontaneous HCV clearance.conclusIons In HD patients, the IFNL3 polymorphisms do not affect anti-HBs development in response to HBV infection or vaccination, but might be involved in the resolution of HCV infection. 895uremic conditions. Therefore, we aimed to show whether the SNPs of IFNL3 might be associated with the development of antibodies to HBV surface antigen (anti-HBs) in response to HBV vaccination or infection as well as with spontaneous HCV clearance in HD patients. PAtIents And methods Patients and controlsThe study included 1110 patients on renal replacement therapy (RRT). They were recruited from 21 dialysis centers located in the Greater Poland region of Poland. The enrollment was started in January, 2009, and finished in May, 2014. All patients were treated with HD on enrollment; however, 28 subjects (2.5%) started RRT with peritoneal dialysis. Subjects dually infected with HBV and HCV or those infected with human immunodeficiency virus were excluded from the study. Of the whole group, 63 patients were HCV-infected (showed antibodies to HCV, anti-HCV) but only 39 of the 63 showed positive for HCV RNA. The remaining 1047 patients were anti-HCV negative, of whom 806 had no history of HBV infection, while 241 were HBV-infected (showed total antibodies to the core antigen of HBV, anti-HBc). In the latter group, 186 subjects developed anti-HBs. HD patient groups are shown in FIGure 1.Subjects were included into th...

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“…Probably, the immunomodulatory effect of IFN can persist even after the end of therapy leading to considerable HBsAg clearance rates. In particular, patients carrying ILİstanbul Med J 2017; 18: 189-95 (34). However, these findings are still a subject of debate, since other studies reported no association between treatment outcome or spontaneous HBsAg seroclearance with rs12979860 polymorphism in both HBeAg-positive and -negative CHB patients (35,36).…”

Section: Current Available Drugsmentioning

confidence: 99%

Chronic Hepatitis B Treatment: Current Perspectives on Telbivudine

Caviglia¹,

Rosso²,

Olivero³

et al. 2017

Istanbul Med J

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Hepatitis B virus (HBV) is a small-enveloped DNA virus that belongs to the Hepadnaviridae family, representing the second greatest cause of chronic viral hepatitis worldwide (1). Despite decades of vaccination, HBV infection is still a major global burden, with 257 million persons chronically infected and approximately 880,000 deaths per year (2). Chronic hepatitis B (CHB) is the result of an acute, unresolved infection that induces an immune-mediated liver damage followed by fibrotic tissue deposition leading overtime to a complete alteration of the hepatic architecture toward cirrhosis and its complications, such as liver failure and hepatocellular carcinoma (HCC) (3, 4).Remarkable advances have been made in the setting of CHB treatment (5). In particular, the development of new molecular biology techniques in association with an ever deeper understanding of the different phases of HBV infection and primarily the introduction of nucleos(t)ide analogs (NAs) are the main features that may lead to the virological cure in the near term and the functional cure in the long-term follow-up (6).This review discusses the current available drugs and treatment guidelines for CHB therapy focusing on telbivudine (LtD), a thymidine analog that has demonstrated unique features that make the abovementioned drug still valid even in the era of new powerful anti-viral agents. HBV Virology and Replication CycleHBV structure Hepatitis B virus structure consists of an outer envelope made of three viral surface proteins named preS1 (large), preS2 (middle), and S (small), which correspond to the serologic HBsantigen (HBsAg), and an inner nucleocapsid formed by core proteins, which correspond to HBcore-antigen (HBcAg) (7). Within the nucleocapsid is present the full-length HBV genome as a partially double-stranded relaxed circular (rc) DNA linked to the viral polymerase protein by a phosphotyrosine bond (8). The genome has an extremely compact organization displaying four partially overlapped major open reading frames (ORFs): the preS/S that encodes the three viral surface proteins, the pre-core/core that encodes both the nucleocapsid core protein and the non-structural core protein known as the e-antigen (HBeAg); the polymerase ORF that encodes the viral polymerase; and the X ORF that encodes the regulatory X protein that is essential for viral replication (9). Chronic Hepatitis B Treatment: Current Perspectives on TelbivudineHepatitis B virus (HBV) is the primary cause of chronic viral hepatitis worldwide. Currently, there are 5 oral nucleos(t)ide analogs (NAs) approved for chronic hepatitis B (CHB) treatment and include lamivudine, adefovir, telbivudine (LtD), entecavir (ETV), and tenofovir disoproxil fumarate (TDF). ETV and TDF are those with higher anti-viral efficacy and lower resistance rates, whereas LtD shows similar efficacy but has a higher risk for viral resistance in long-term monotherapy. However, LtD carries several advantages that must be considered and are worthy of discussion. Compared to other NAs, LtD showed a poten...

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IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B

Cited by 156 publications

References 35 publications

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

Effect of interferon λ3 gene polymorphisms, rs8099917 and rs12979860, on response to hepatitis B virus vaccination and hepatitis B or C virus infections among hemodialysis patients

Chronic Hepatitis B Treatment: Current Perspectives on Telbivudine

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